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1.
J Geriatr Psychiatry Neurol ; 36(5): 407-416, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36592403

RESUMO

OBJECTIVE: Geriatric patients account for a significant proportion of the collective treated by psychiatric consultation service in hospitals. In the Emergency Department (ED), psychotropic drugs are frequently recommended, notwithstanding their extensive side-effect profiles. This study sought to investigate medication safety of geriatric patients referred to psychiatric consultation service in the ED. METHODS: Medication lists of 60 patients from the general internal medicine and trauma surgery EDs referred to psychiatric consultation service were analyzed. Utilizing PRISCUS list and Fit fOR The Aged (FORTA) classification, prescriptions of potentially inappropriate medications (PIMs) were assessed. RESULTS: 84 drugs were newly prescribed following psychiatric consultations. The total number of drugs per patient was 5.4 ± 4.2 before psychiatric consultation and 6.5 ± 4.2 thereafter (p < .001). 22.6 % of the newly recommended drugs were PIMs according to the PRISCUS list, while 54.8 % were designated as therapeutic alternatives to PIMs. 54.8 % and 20.2 % of the newly recommended drugs were FORTA category C and D drugs, respectively. An average of 1.2 ± 1.7 drug-drug interactions (DDIs) existed before psychiatric consultation and 1.3 ± 1.9 DDIs thereafter (p = .08). CONCLUSION: The majority of newly recommended drugs by psychiatric consultation service in the ED were designated as suitable therapeutic alternatives to PIMs according to the PRISCUS list, but had comparatively unfavorable ratings according to the FORTA classification, demonstrating discrepancies between these two PIM classification systems. Physicians delivering psychiatric consultation services in the ED should not solely rely on one PIM classification system.


Assuntos
Prescrição Inadequada , Psiquiatria , Humanos , Idoso , Estudos Retrospectivos , Lista de Medicamentos Potencialmente Inapropriados , Serviço Hospitalar de Emergência
2.
Eur J Clin Pharmacol ; 79(2): 207-217, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36478283

RESUMO

PURPOSE: To determine the nature and frequency of duplicate prescriptions (DPs) in the emergency department (ED) by utilization of a novel categorization of DPs which differentiates between appropriate DPs (ADPs) and potentially inappropriate DPs (PIDPs). METHODS: In this retrospective cohort study, adult patients who presented to the ED for internal medicine of a large university hospital in northern Germany in 2018 and 2019 were screened for the presence of DPs. Descriptive statistical methods were used to characterize the nature and frequency of PIDPs compared to the frequency of ADPs. RESULTS: A total of 4208 patients were enrolled into the study. The median age of the study population was 63 years (interquartile range (IQR) 48-77), 53.9% were female. The patients took a median of 5 drugs (IQR 3-9). 10.9% of the study population were affected by at least one PIDP (at least one grade-1 PIDP: 6.1%; at least one grade-2 PIDP: 4.5%; at least one grade-3 PIDP: 1.1%). Non-opioid analgesics accounted for the majority of grade-1 PIDPs, while inhalatives were most frequently responsible for grade-2 and grade-3 PIDPs. Nearly half of the study population (48.6%) displayed at least one ADP. CONCLUSION: PIDPs pose a frequent pharmacological challenge in the ED. The medication review should comprise a systematic screening for PIDPs with a particular focus on non-opioid analgesics and inhalatives. ADPs were detected more frequently than PIDPs, questioning the predominant notion in the medical literature that DPs are exclusively deleterious.


Assuntos
Analgésicos não Narcóticos , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Analgésicos não Narcóticos/uso terapêutico , Prescrição Inadequada , Prescrições de Medicamentos , Serviço Hospitalar de Emergência , Analgésicos Opioides/uso terapêutico , Padrões de Prática Médica
3.
BMC Psychiatry ; 23(1): 279, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081424

RESUMO

BACKGROUND: Differentiating depression and dementia in elderly patients represents a major clinical challenge for psychiatrists. Pharmacological and non-pharmacological treatment options for both conditions are often used cautiously due to fear of adverse effects. If a clinically indicated therapy is not initiated due to fear of adverse effects, the quality of life of affected patients may significantly be reduced. CASE PRESENTATION: Here, we describe the case of a 65-year-old woman who presented to the department of psychiatry of a university hospital with depressed mood, pronounced anxiety, and nihilistic thoughts. While several pharmacological treatments remained without clinical response, further behavioral observation in conjunction with 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed the diagnosis of frontotemporal dementia (FTD). To counter the pharmacological treatment resistance of psychotic depression, we decided to perform electroconvulsive therapy (ECT). Remarkably, ten sessions of ECT yielded an almost complete remission of depressive symptoms. In addition, the patient's delusional ideas disappeared. A follow-up 18F-FDG PET/CT after the ECT series still showed a frontally and parieto-temporally accentuated hypometabolism, albeit with a clear regression compared to the previous image. The follow-up 18F-FDG PET/CT thus corroborated the diagnosis of FTD, while on the other hand it demonstrated the success of ECT. CONCLUSIONS: In this case, ECT was a beneficial treatment option for depressive symptoms in FTD. Also, 18F-FDG PET/CT should be discussed as a valuable tool in differentiating depression and dementia and as an indicator of treatment response.


Assuntos
Eletroconvulsoterapia , Demência Frontotemporal , Feminino , Humanos , Idoso , Demência Frontotemporal/complicações , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/terapia , Glucose , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Depressão/complicações , Depressão/terapia , Qualidade de Vida , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos
4.
Alcohol Alcohol ; 58(2): 216-223, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36747480

RESUMO

AIMS: The dopamine receptor D2 (DRD2) is substantially involved in several forms of addiction. In addition to genetic polymorphisms, epigenetic mechanisms have emerged as an important means of regulation. Previously, DRD2 hypo- and hyper-methylation have been observed in alcohol use disorder (AUD). Blood samples are commonly used as a surrogate marker of epigenetic alterations in epigenetic research, but few specific comparisons between blood and brain tissue samples in AUD exist. METHODS: We used post-mortem brain tissue samples of 17 deceased patients with AUD and 31 deceased controls to investigate the relationship between blood and brain methylation of the DRD2 promoter. RESULTS: When investigating individual cytosine methylation sites (CpG), several significant differences were found in the nucleus accumbens and hippocampus in the study population. Investigating binding sites with significant differences in methylation levels revealed hypomethylated CpGs targeting mainly activating transcription factors. CONCLUSION: These findings support an altered transcription of the DRD2 gene in AUD specimens with a consecutively changed reward response in the brain. While methylation between specific brain regions and blood is comparable, our study further suggests that blood methylation cannot provide meaningful perspectives on DRD2 promoter methylation in the brain.


Assuntos
Alcoolismo , Receptores de Dopamina D2 , Humanos , Consumo de Bebidas Alcoólicas , Alcoolismo/genética , Encéfalo/metabolismo , Metilação de DNA , Epigênese Genética , Receptores de Dopamina D2/genética
5.
Int J Psychiatry Med ; : 912174231177230, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194304

RESUMO

OBJECTIVE: Psychiatric patients in general, and elderly psychiatric patients in particular, are at risk of adverse drug reactions due to comorbidities and inappropriate polypharmacy. Interdisciplinary and clinical-pharmacologist-led medication reviews may contribute to medication safety in the field of psychiatry. In this study, we reported the frequency and characteristics of clinical-pharmacological recommendations in psychiatry, with a particular focus on geriatric psychiatry. METHOD: A clinical pharmacologist, in collaboration with the attending psychiatrists and a consulting neurologist, conducted interdisciplinary medication reviews in a general psychiatric ward with a geropsychiatric focus at a university hospital over a 25-week period. All clinical and pharmacological recommendations were recorded and evaluated. RESULTS: A total of 316 recommendations were made during 374 medication reviews. Indications/contraindications of drugs were the most frequently discussed topics (59/316; 18.7 %), followed by dose reductions (37/316; 11.7 %), and temporary or permanent discontinuation of medications (36/316; 11.4 %). The most frequent recommendations for dose reduction involvedbenzodiazepines (9/37; 24.3 %). An unclear or absent indication was the most common reason for recommending temporary or permanent discontinuation of the medication (6/36; 16.7 %). CONCLUSION: Interdisciplinary clinical pharmacologist-led medication reviews represented a valuable contribution to medication management in psychiatric patients, particularly the elderly ones.

6.
Psychother Psychosom Med Psychol ; 73(5): 173-179, 2023 May.
Artigo em Alemão | MEDLINE | ID: mdl-36195103

RESUMO

OBJECTIVE: In addition to teaching theoretical and clinical-practical skills, the development of individual moral competence should be another core concern in medical school. However, research suggests that moral competence in students of human medicine stagnates or even declines during the course of medical school. Therefore, the present cross-sectional study investigated the moral competence of medical students at the beginning of their studies and during their practical year, as well as the effects of testosterone as a neurohormone on moral judgment. METHODS: By means of a cross-sectional study, the moral judgment ability of 24 first-year and 16 practical year students of Hannover Medical School was recorded and evaluated with the Moral Competence Test (MCT) according to Lind. The testosterone serum level of the study participants was statistically related to the MCT results. RESULTS: No significant differences between first-year (mean±standard deviation (SD): 13.16±8.21) and practical year students (mean±SD: 11.24±8.07) with regard to moral competence as per the MCT were identified (p=0.36). Higher serum testosterone levels did not show a statistically significant correlation with moral competence (r=-0.09, p=0.58). CONCLUSION: Our results do not show a clear trend whether moral competence is lower in medical students in advanced semesters compared to the beginning of medical school and whether moral competence is influenced by the neurohormone testosterone. Nevertheless, it seems reasonable to implement moral competence training for medical students early, continuously, and as individually designed as possible during medical school (and to evaluate it in further studies) in order to preventively counteract stagnation or regression of moral judgment.


Assuntos
Estudantes de Medicina , Humanos , Estudos Transversais , Princípios Morais , Julgamento , Avaliação Educacional
7.
Psychogeriatrics ; 23(2): 354-363, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36720843

RESUMO

BACKGROUND: This study sought to investigate the frequency and characteristics of duplicate prescriptions (DPs) in elderly psychiatric inpatients using a novel categorisation of DPs that differentiates between appropriate duplicate prescriptions (ADPs) and potentially inappropriate duplicate prescriptions (PIDPs). METHODS: The study was conducted as a monocentric retrospective cross-sectional pilot study on the gerontopsychiatric ward of the Department of Psychiatry, Social Psychiatry and Psychotherapy of Hannover Medical School, a large university hospital in northern Germany. The outcome measures were the nature and frequency of PIDPs compared with the frequency of ADPs. RESULTS: For 92 individual patients a total of 339 medication chart reviews were conducted between April 2021 and February 2022. The median age of the study population was 73 years (interquartile range (IQR) 68-82 years); 64.6% were female. Patients' medications comprised a median of eight drugs (IQR 6-11 drugs) and 43.1% of the study population were exposed to at least one PIDP (at least one grade-1 PIDP: 39.5%; at least one grade-2 PIDP: 5.0%; at least one grade-3 PIDP: 1.5%). Sedatives were most frequently responsible for grade-1 and grade-2 PIDPs, while grade-3 PIDPs were elicited exclusively by analgesics. Nearly half of the study population (49.0%) displayed at least one ADP. CONCLUSION: Even though the clinical implications of PIDPs are not fully established to date, we recommend that physicians who treat elderly psychiatric patients pay special attention to PIDPs, especially PIDPs elicited by sedatives. Termination of PIDPs may prevent adverse drug reactions and save healthcare expenditures.


Assuntos
Psiquiatria Geriátrica , Hipnóticos e Sedativos , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Transversais , Estudos Retrospectivos , Projetos Piloto , Prescrições , Analgésicos , Prescrições de Medicamentos
8.
J Neural Transm (Vienna) ; 129(11): 1367-1375, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36050603

RESUMO

Adverse drug reactions (ADRs) constitute a frequent cause of hospitalization in older people. The risk of ADRs is increased by the prescription of potentially inappropriate medications for older people (PIMs). The PRISCUS list and the FORTA classification represent established tools to detect PIMs. The aim of the present study was to examine the prevalence and characteristics of PIM prescriptions on the gerontopsychiatric ward of a university hospital in Germany. To this aim, medication charts of 92 patients (mean age 75.9 ± 7.7 years; 66.3% female) were analyzed on a weekly basis until patient discharge by utilization of the PRISCUS list and the FORTA classification. Overall, 335 medication reviews comprising 2363 drug prescriptions were analyzed. 3.0% of the prescribed drugs were PIMs according to the PRISCUS list, with benzodiazepines and Z-drugs accounting for nearly half (49.3%) of all PIM prescriptions. 30.4% of the patients were prescribed at least one PRISCUS-PIM, while 43.5% of the study population took at least one FORTA class D drug. A considerable proportion of gerontopsychiatric patients were affected by PIMs; however, the overall number of PIM prescriptions in the study population was low. Further improvements in the quality of prescribing should target the use of sedating agents such as benzodiazepines and Z-drugs. Physicians should be aware of discrepancies between the PRISCUS list and the FORTA classification.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Idoso de 80 Anos ou mais , Benzodiazepinas , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Psiquiatria Geriátrica , Humanos , Prescrição Inadequada , Masculino
9.
Artigo em Inglês | MEDLINE | ID: mdl-36005273

RESUMO

OBJECTIVES: Information on medication-related problems (MRPs) in elderly psychiatric patients is scarce. In the present study, we analyzed the frequency and characteristics of MRPs in patients ≥60 years treated on the gerontopsychiatric ward of Hannover Medical School in 2019. METHODS: Taking advantage of an interdisciplinary approach, two independent investigators screened hospital discharge letters of 230 psychiatric inpatients for clinically relevant MRPs, followed by validation through an interdisciplinary expert panel. Drug interactions as a subset of MRPs were analyzed with the aid of two different drug interaction programs. RESULTS: 230 patients (63.0% female, mean age 73.7 ± 8.4 years, median length of stay 18 days) were prescribed a median of 6 drugs. In total, 2180 MRPs were detected in the study population and 94.3% of the patients exhibited at least one MRP. Patients displayed a median of 7 MRPs (interquartile range 3-15). Pharmacodynamic interactions accounted for almost half of all MRPs (48.1%; 1048/2180). The number of drugs prescribed and the number of MRPs per patient showed a strong linear relationship (adjusted R2  = 0.747). CONCLUSION: An exceedingly high proportion of elderly psychiatric inpatients displayed clinically relevant MRPs in the present study, which may be explained by the multimorbidity prevalent in the study population and the associated polypharmacy. The number of drug interactions was largely in accordance with previous studies. As a novel finding, we detected that a considerable proportion of elderly psychiatric inpatients were affected by potential prescribing omissions, potentially inappropriate duplicate prescriptions, and insufficient documentation.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Feminino , Psiquiatria Geriátrica , Humanos , Prescrição Inadequada , Masculino , Polimedicação , Estudos Retrospectivos
10.
Internist (Berl) ; 63(5): 545-550, 2022 May.
Artigo em Alemão | MEDLINE | ID: mdl-35195756

RESUMO

Here, we report on a patient with deep vein thrombosis of the right leg, in whom diagnostic work-up revealed a previously unknown chondrosarcoma of the tibia. Physical examination revealed a firm, nondisplaceable mass on the dorsal side of the right knee that appeared as a cystic formation on ultrasound. X­ray, computed tomography, and magnetic resonance imaging were consistent with chondrosarcoma, which had likely provoked the thrombosis by local compression or paraneoplastic mechanisms. After resection of the tumor, anticoagulation was continued. In a review of all findings, a final diagnosis of highly differentiated chondrosarcoma with thrombosis of the popliteal vein was made.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Trombose , Trombose Venosa , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/cirurgia , Humanos , Ultrassonografia/métodos , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia
11.
Neuropsychobiology ; 80(1): 36-44, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32599581

RESUMO

BACKGROUND: Patients suffering from schizophrenic psychosis show reduced synaptic connectivity compared to healthy individuals. Furthermore, the use of cannabis often precedes the onset of schizophrenic psychosis. Therefore, we investigated whether consumption of cannabis has an impact on the methylation pattern of schizophrenia candidate genes concerned with the development and preservation of synapses and synaptic function. METHODS: Fifty blood samples of outpatients affected by treatment-resistant schizophrenic psychosis were collected in the outpatient department of Ch Ste Anne/INSERM (Paris, France). Extracted DNA was sent to the LMN/MHH (Hanover, Germany) where DNA samples were bisulfite converted. The methylation patterns of the promoter region of neuregulin 1 (NRG1), neurexin (NRXN1), disrupted in schizophrenia 1 (DISC1), and microtubule-associated-protein tau (MAPT) were then analysed by sequencing according to Sanger. RESULTS: In NRXN1 the group of non-consumer patients showed a methylation rate slightly lower than controls. In patients with preliminary use of tetrahydrocannabinol (THC) the NRXN1 promoter turned out to be methylated almost two times higher than in non-consumer patients. In MAPT, non-consumer patients showed a significant lower mean methylation rate in comparison to controls. In THC-consuming patients the difference compared with controls became less. NRG1 and DISC1 showed no significant differences between groups, whereas DISC1 appeared to be not methylated at all. CONCLUSION: In MAPT and NRXN1 mean methylation rates were lower in non-consumer patients compared with controls, which seems to be a compensatory mechanism. With consumption of THC, mean methylation rates were increased: in the case of MAPT compared with controls, and in NRXN1 even significantly beyond that. Methylation of NRG1 and DISC1 seems not to be affected by the psychiatric disorder or by consumption of THC.


Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Metilação de DNA/efeitos dos fármacos , Dronabinol/farmacologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Esquizofrenia/sangue , Adulto , Proteínas de Ligação ao Cálcio/metabolismo , Feminino , Humanos , Masculino , Proteínas do Tecido Nervoso/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Neuregulina-1/metabolismo , Proteínas tau/metabolismo
12.
Neuropsychobiology ; 80(1): 64-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32659769

RESUMO

BACKGROUND/AIMS: Opioid dependence is a severe disease which is associated with a high risk of relapse, even in cases of successful withdrawal therapy. Studies have shown alterations of the hypothalamic-pituitary-gonadal axis in opioid-dependent patients, such as decreased testosterone serum levels in affected males. Sex hormones and the steroid 5-alpha-reductase 2 (SRD5A2) V89L polymorphism are associated with craving during alcohol withdrawal, but little is known about their impact on symptomatology of opioid dependence. METHODS: In this study, we analyzed 2 independent male cohorts of opioid-dependent patients for possible alterations in testosterone serum levels compared to non-opioid-dependent controls. In one of the cohorts, we additionally investigated associations of testosterone serum levels and 3 SRD5A2 polymorphisms with symptoms of opioid dependence, measured by the Heroin Craving Questionnaire (HCQ). RESULTS: In the patient groups, we found significantly decreased testosterone serum levels compared to the control groups. Furthermore, we found significant associations of both the testosterone serum levels and the SRD5A2 V89L polymorphism with opioid craving assessed by the HCQ. CONCLUSION: Our data show a possible role of testosterone metabolism in opioid dependence, which may be relevant for the establishment of future treatment strategies.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Fissura/fisiologia , Proteínas de Membrana/genética , Transtornos Relacionados ao Uso de Opioides/sangue , Transtornos Relacionados ao Uso de Opioides/genética , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Testosterona/sangue , Adulto , Estudos de Coortes , Humanos , Masculino , Polimorfismo Genético
13.
Eur Addict Res ; 26(2): 103-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940647

RESUMO

AIMS: Childhood trauma is of importance for the manifestation of substance-related disorders and maintenance of hypothalamic-pituitary-adrenal (HPA)-axis disorders. Since stress plays a crucial role in opioid compliance and craving, we investigated the immediate effects of diacetylmorphine application on the HPA axis. In particular, adrenocorticotropic hormone (ACTH) and cortisol secretion, as well as satiety regulating proopiomelanocortin peptides α-melanocyte-stimulating hormone (MSH) and ß-endorphin (END) in a cohort of opioid-dependent patients in diamorphine maintenance treatment concerning the clinical severity of their childhood trauma. METHODS: We compared the serum levels of ACTH, cortisol, MSH, and END in 15 opioid-dependent patients. All participants received treatment with diamorphine and were observed at 5 timepoints before and after injection. We split the cohort into 2 subgroups concerning childhood trauma measured by the Childhood Trauma Questionnaire. RESULTS: Splitting in 2 subgroups for mild (5) and severe trauma (10), we found that while both groups show a significant reduction of ACTH and cortisol levels over time, slopes display different progressions over time for cortisol (F[1.6] = 9.38, p = 0.02), while remaining identical for ACTH (F[1.6] = 1.69, p = 0.24). Also, levels of both MSH and END were significantly lower in severely traumatized patients. CONCLUSIONS: For the first time, we present a detailed representation of stress- and addiction-related proteins for the first 5 h after diamorphine application, demonstrating the interrelationship between stress hormones and childhood trauma as well as its potential effects on the progression of addictions such as opioid dependence.


Assuntos
Experiências Adversas da Infância , Dependência de Heroína , Heroína , Estresse Psicológico/psicologia , Ferimentos e Lesões/psicologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Criança , Estudos de Coortes , Feminino , Heroína/farmacologia , Heroína/uso terapêutico , Dependência de Heroína/tratamento farmacológico , Dependência de Heroína/metabolismo , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Inquéritos e Questionários/estatística & dados numéricos , beta-Endorfina/sangue
14.
Neuropsychobiology ; 75(4): 193-199, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29510398

RESUMO

The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro- opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.


Assuntos
Metilação de DNA/efeitos dos fármacos , Dependência de Heroína/tratamento farmacológico , Heroína/administração & dosagem , Entorpecentes/administração & dosagem , Pró-Opiomelanocortina/genética , Receptores de Glucocorticoides/genética , Administração Intravenosa , Adulto , Estudos Cross-Over , Emoções/efeitos dos fármacos , Emoções/fisiologia , Epigênese Genética/efeitos dos fármacos , Feminino , Dependência de Heroína/genética , Dependência de Heroína/metabolismo , Dependência de Heroína/psicologia , Humanos , Masculino , Pró-Opiomelanocortina/metabolismo , Regiões Promotoras Genéticas , Receptores de Glucocorticoides/metabolismo , Fatores de Tempo , Resultado do Tratamento
15.
Eur Arch Psychiatry Clin Neurosci ; 267(1): 33-40, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26801497

RESUMO

Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = -0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck's Depression Inventory measurements (r = -0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. levomethadone with heroine co-use: p = 0.043, diamorphine vs. levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving levomethadone without heroine co-use (linear mixed model: control vs. levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in levomethadone maintenance treatment.


Assuntos
Analgésicos Opioides/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/sangue , Heroína/uso terapêutico , Metadona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/sangue , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Adulto , Analgésicos Opioides/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Estudos de Casos e Controles , Depressão/etiologia , Epigênese Genética/efeitos dos fármacos , Feminino , Heroína/farmacologia , Humanos , Masculino , Metadona/farmacologia , Metilação/efeitos dos fármacos , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/psicologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Inquéritos e Questionários , Escala Visual Analógica
16.
Alcohol Alcohol ; 52(3): 277-281, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28430931

RESUMO

AIMS: Neurotrophins have been linked to the symptomatology of alcohol dependence. We aimed to investigate a possible association between the methylation of the promoters of both neurotrophins, the serum levels of the cytokines and core symptoms of alcohol dependence as withdrawal severity and anxiety. METHODS: In this study we investigated a possible association between alterations in the methylation of the BDNF IV/NGF I gene promoter and the cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in 55 male alcohol-dependent patients. RESULTS: Mean methylation of the promoter of the BDNF gene was significantly associated with the TNF-α serum levels and the CIWA-score during withdrawal (P < 0.001). Moreover, mean methylation of the NGF I promoter was significantly associated with the IL-6 serum levels and STAI-I score during withdrawal (P < 0.001). CONCLUSION: Our results suggest an association between the epigenetic regulation of both neurotrophins, BDNF and NGF, cytokine release and the symptomatology of alcohol dependence. They imply that changes in the methylation of neurotrophins may contribute to the symptomatology of alcohol dependence by affecting relevant downstream signaling cascades.


Assuntos
Sintomas Afetivos/genética , Sintomas Afetivos/psicologia , Alcoolismo/genética , Alcoolismo/psicologia , Citocinas/fisiologia , Epigênese Genética/genética , Fatores de Crescimento Neural/fisiologia , Transdução de Sinais/genética , Adulto , Sintomas Afetivos/etiologia , Fator Neurotrófico Derivado do Encéfalo/genética , Depressores do Sistema Nervoso Central/metabolismo , Metilação de DNA , Etanol/metabolismo , Feminino , Humanos , Interleucina-6/genética , Masculino , Modelos Psicológicos , Fator de Crescimento Neural/genética , Testes Neuropsicológicos , Síndrome de Abstinência a Substâncias/genética , Síndrome de Abstinência a Substâncias/psicologia , Fator de Necrose Tumoral alfa/genética
17.
Eur Addict Res ; 23(5): 249-259, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29224006

RESUMO

AIMS: The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis. METHODS: We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or levomethadone (n = 54) and similar levels in a healthy control group (n = 72). RESULTS: There was a significantly higher methylation of VEGF-A in opioid-maintained patients with levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001). CONCLUSIONS: The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.


Assuntos
Epigênese Genética/efeitos dos fármacos , Fator de Crescimento Neural/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides , Regiões Promotoras Genéticas/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Adulto , Analgésicos Opioides/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Feminino , Heroína/farmacologia , Heroína/uso terapêutico , Humanos , Masculino , Metadona/farmacologia , Metadona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
19.
Front Psychiatry ; 14: 1272695, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264634

RESUMO

Introduction: Older patients are frequently affected by infectious diseases and adverse drug reactions (ADRs) of consecutively prescribed antibiotics. Particularly within geriatric psychiatry, high rates of potentially inappropriate prescriptions (PIPs) have been described, significantly complicating pharmacological treatment. Therefore, this study aimed to investigate the frequency and characteristics of antibiotic PIPs in geriatric psychiatry. Methods: Medication charts of 139 patient cases (mean age 78.8 years; 69.8% female) receiving antibiotic treatment on a geriatric psychiatric ward were analyzed. Utilizing previously published definitions of antibiotic PIPs, adequacy of the antibiotic prescriptions was subsequently assessed. Results: 16.3% of all screened patient cases (139/851) received an antibiotic treatment during their inpatient stay. 59.5% of antibiotic prescriptions were due to urinary tract infections, followed by pulmonary (13.3%) and skin and soft tissue infections (11.3%). 46.7% of all antibiotic prescriptions fulfilled at least one PIP criterium, with the prescription of an antibiotic course for more than seven days as the most common PIP (15.3%). Discussion: Antibiotic PIPs can be considered as a frequent phenomenon in geriatric psychiatry. Especially the use of fluoroquinolones and cephalosporins should be discussed critically due to their extensive side effect profiles. Due to the special characteristics of geriatric psychiatric patients, international guidelines on the use of antibiotics should consider frailty and psychotropic polypharmacy of this patient population more closely.

20.
Ir J Med Sci ; 192(6): 2917-2927, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36807758

RESUMO

OBJECTIVE: To investigate the frequency and characteristics of adverse drug reactions (ADRs) that occurred on the gerontopsychiatric ward of Hannover Medical School over a 6-year period. DESIGN: Retrospective monocentric cohort study. RESULTS: Six hundred thirty-four patient cases (mean age 76.6 ± 7.1 years; 67.2% female) were analysed. In total, 92 ADRs in 56 patient cases were registered in the study population. The overall ADR prevalence, the ADR prevalence upon hospital admission, and the ADR prevalence during hospitalisation were 8.8%, 6.3%, and 4.9%, respectively. The most frequent ADRs were extrapyramidal symptoms, alterations in blood pressure or heart rate, and electrolyte disturbances. Of note, two cases of asystole and one case of obstructive airway symptoms related to general anaesthesia in the context of electroconvulsive therapy (ECT) were detected. The presence of coronary heart disease was associated with an increased risk of ADR occurrence (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.37-6.22), while the presence of dementia was associated with a decreased risk of ADR development (OR 0.45, 95% CI 0.23-0.89). CONCLUSIONS: Type and prevalence of ADRs in the present study were largely in accordance with previous reports. By contrast, we did not observe a relationship between advanced age or female sex and ADR occurrence. We detected a risk signal for cardiopulmonary ADRs related to general anaesthesia in the context of ECT that warrants further investigation. Elderly psychiatric patients should be carefully screened for cardiopulmonary comorbidities before initiation of ECT.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Psiquiatria Geriátrica , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Estudos de Coortes , Estudos Prospectivos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hospitalização
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